The Programmable Implantable Medication System (PIMS) is a variable rate, remotely programmable infusion pump with battery life expectancy exceeding 12 years. This study will test the longterm function of PIMS in dogs, and determines its usefulness as a means of treating diabetes in humans. We will also use PIMS to answer certain questions concerning the chronic complications of diabetes. Work in progress has already demonstrated the safety of PIMS, and its efficacy in controlling the plasma glucose (PG) of dogs for up to 18 months. This project will determine whether it can operate effectively over a five year period, in dogs and in humans. Using PIMS as a research tool, we will determine its effect on the longterm complications of diabetes by maintaining four sets of dogs, 6 in each group: non-diabetics (PG, in our hands, 83 plus and minus 10 mg/dl (SD)); diabetics maintained with PIMS in very good control (99 plus and minus 49 mg/dl); diabetics maintained in optimal control with subcutaneous insulin (175 plus and minus 109 mg/dl) and diabetics kept in poor diabetic control (300-400 mg/dl). Detailed and sensitive methods will be applied to evaluate the development of diabetic retinopathy, cardiac function, atherosclerosis, and neuropathy. Retinopathy will be followed yearly by fundus photography and fluorescein angiography; the effect of lens extraction will be tested; detailed pathologic examination of the eyes will be made postmortem. Cardiac left ventricular function will be tested by a computerized multiple marker imaging system, as well as by left sided cardiac catheterization. Atherosclerosis will be measured quantitatively at postmortem. Neuropathy will be evaluated by morphometometry on nerve biopsy as well as by nerve conduction velocities. A series of studies will be done to determine the effect of manipulations of diet and insulin on lipid metabolism. The project, then, will 1) test the longterm feasibility of treating experimental diabetes in dogs with PIMS; 2) use that pump to test the hypothesis that good control minimizes diabetic complications; 3) determine PIMS' effect on abnormalities in lipid metabolism associated with diabetes; and 4) test whether PIMS can be used safely and effectively to control diabetes in humans.